Principal Investigator/Program Director (Last, First, Middle):
Chigaev, Alexandre
BIOGRAPHICAL SKETCH
Provide the following information for the Senior key personnel and other significant contributors in order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Chigaev, Alexandre
Research Assistant Professor of Pathology
eRA COMMONS USER NAME
ACHIGAEV
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
Saratov State University, Saratov, Russia
Moscow State University, Moscow, Russia
Weizmann Institute of Science, Rehovot,
Israel
University of New Mexico
and Los Alamos National Laboratory, NM
B.S. and M.S.
Ph.D.
1983-1990
1990-1994
Biology
Biology
Postdoctoral
1998-2000
Biochemistry
Postdoctoral
2000-2003
Pathology
Flow Cytometry
A. Personal Statement
More than a decade ago in collaboration with Dr. Larry A. Sklar I pioneered a novel approach to the
studies of cell adhesion molecules (integrins) through the use of small ligand-mimicking fluorescent
probes. This approach vastly expanded our understanding of the regulation of one of the major leukocyte
integrins, Very Late Antigen-4. For the current application, we propose to focus on the specialization of
integrin-dependent adhesion using a set of novel tools, developed to specifically target another leukocyte
integrin - Leukocyte Function-associated Antigen 1 (LFA-1). This innovation will allow us to follow rapid
LFA-1 conformational changes in response to cell signaling on live immune cells in real-time at natural
receptor abundance. To our best knowledge this is possible only using our current technology.
Conformational regulation of LFA-1 provides a basis for the interaction of immune cells, modulation of
immune responses, and it is implicated in a large number of pathologies.
B. Positions and Honors
Positions and Employment
1990-1991
Director, Laboratory of Biochemistry and Physiology Dept., Vavilov's State Agricultural
University, Saratov, Russia
1991-1995
Lecturer, Department of Biochemistry and Physiology, Vavilov's State Agricultural University,
Saratov, Russia
1995-1998
Referee, Biological Abstract, Moscow, Russia
1997-1998
Senior Lecturer, Department of Biochemistry and Physiology, Vavilov's State Agricultural
University, Saratov, Russia
1997-1998
Assistant Professor, Department of Biochemistry and Physiology, Vavilov's State Agricultural
University, Saratov, Russia
2003-2006
Senior Research Scientist, Cancer Research and Treatment Center, University of New Mexico,
Albuquerque, NM
2006-2007
Visiting Research Assistant Professor, Department of Pathology, School of Medicine, University
of New Mexico, Albuquerque, NM
2007Research Assistant Professor, Department of Pathology, School of Medicine, University of New
Mexico, Albuquerque, NM
PHS 398/2590 (Rev. 06/09)
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Biographical Sketch Format Page
Principal Investigator/Program Director (Last, First, Middle):
Chigaev, Alexandre
Other Experience and Professional Memberships
1985-1986
Trainee, Laboratory of Hematology, Tbilisi Military Hospital, Tbilisi, Georgia
1987
Summer School, Biophysics, Moscow State University, Russia
1988
Summer School, Biophysics, Moscow State University, Russia
1987
Trainee, Biophysics, Moscow State University, Russia
1998
Sabbatical, Nonlinear Dynamics, Saratov State University, Russia
1998
Karyn Kupcinet International Science School, Biochemistry, Weizmann Institute of Science,
Rehovot, Israel
2004Member, American Society for Cell Biology (ASCB)
2010Member, American Society for Biochemistry and Molecular Biology (ASBMB)
2002Ad hoc Reviewer: The Journal of Biological Chemistry, The Journal of Immunology, BMC
Immunology, Biochemistry
Honors
1990
M.S. (Summa Cum Laude), Saratov State University, Russia
C . Selected Peer-reviewed Publications
Most relevant to the current application
1. Chigaev, A., Y. Smagley, Y. Zhang, A. Waller, M. K. Haynes, O. Amit, W. Wang, R. S. Larson, and L. A.
Sklar. 2011. Real-time Analysis of the Inside-out Regulation of Lymphocyte Function-associated Antigen1 Revealed Similarities to and Differences from Very Late Antigen-4. J.Biol.Chem. 286:20375-20386.
2. Chigaev, A., Y. Wu, D. B. Williams, Y. Smagley, and L. A. Sklar. 2011. Discovery of very late antigen-4
(VLA-4, {alpha}4{beta}1 integrin) allosteric antagonists. J.Biol.Chem. 286:5455-5463.
3. Njus, B. H., A. Chigaev, A. Waller, D. Wlodek, L. Ostopovici-Halip, O. Ursu, W. Wang, T. I. Oprea, C. G.
Bologa, and L. A. Sklar. 2009. Conformational mAb as a tool for integrin ligand discovery. Assay.Drug
Dev.Technol. 7:507-515.
4. Larson, R. S., T. Davis, C. Bologa, G. Semenuk, S. Vijayan, Y. Li, T. Oprea, A. Chigaev, T. Buranda, C.
R. Wagner, and L. A. Sklar. 2005. Dissociation of I domain and global conformational changes in LFA-1:
refinement of small molecule-I domain structure-activity relationships. Biochemistry 44:4322-4331.
5. Chigaev, A., G. Zwartz, S. W. Graves, D. C. Dwyer, H. Tsuji, T. D. Foutz, B. S. Edwards, E. R. Prossnitz,
R. S. Larson, and L. A. Sklar. 2003. Alpha4beta1 integrin affinity changes govern cell adhesion.
J.Biol.Chem. 278:38174-38182.
Additional recent publications of importance to the field
1. Chigaev, A. and L. A. Sklar. 2012. Aspects of VLA-4 and LFA-1 regulation that may contribute to rolling
and firm adhesion. Front. Immun. 3:242. doi: 10.3389/fimmu.2012.00242.
2. Chigaev, A. and L. A. Sklar. 2012. Overview: assays for studying integrin-dependent cell adhesion.
Methods Mol. Biol. 757:3-14.
3. Chigaev, A., Y. Smagley, and L. A. Sklar. 2011. Nitric oxide/cGMP pathway signaling actively downregulates alpha4beta1-integrin affinity: an unexpected mechanism for inducing cell de-adhesion.
BMC.Immunol. 12:28.
4. Chigaev, A., S. S. Winter, and L. A. Sklar. 2011. Is prolonged stem cell mobilization detrimental for
hematopoiesis? Med. Hypotheses 77:1111-1113.
5. Chigaev, A., A. Waller, O. Amit, L. Halip, C. G. Bologa, and L. A. Sklar. 2009. Real-time Analysis of
Conformation-sensitive Antibody Binding Provides New Insights into Integrin Conformational Regulation.
J.Biol.Chem. 284:14337-14346.
6. Chigaev, A., A. Waller, O. Amit, and L. A. Sklar. 2008. Galphas-coupled receptor signaling actively downregulates alpha4beta1-integrin affinity: a possible mechanism for cell de-adhesion. BMC.Immunol. 9:26.
7. Chigaev, A., A. Waller, G. J. Zwartz, T. Buranda, and L. A. Sklar. 2007. Regulation of cell adhesion by
affinity and conformational unbending of alpha4beta1 integrin. J.Immunol. 178:6828-6839.
PHS 398/2590 (Rev. 11/07)
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Principal Investigator/Program Director (Last, First, Middle):
Chigaev, Alexandre
8. Chigaev, A., G. J. Zwartz, T. Buranda, B. S. Edwards, E. R. Prossnitz, and L. A. Sklar. 2004.
Conformational regulation of alpha 4 beta 1-integrin affinity by reducing agents. "Inside-out" signaling is
independent of and additive to reduction-regulated integrin activation. J.Biol.Chem. 279:32435-32443.
9. Zwartz, G., A. Chigaev, T. Foutz, R. S. Larson, R. Posner, and L. A. Sklar. 2004. Relationship between
Molecular and Cellular Dissociation Rates for VLA-4/VCAM-1 Interaction in the Absence of Shear Stress.
Biophys.J. 86:1243-1252.
10. Chigaev, A., T. Buranda, D. C. Dwyer, E. R. Prossnitz, and L. A. Sklar. 2003. FRET detection of cellular
alpha4-integrin conformational activation. Biophys.J. 85:3951-3962.
D. Research Support
Ongoing Research Support
5R01 HL081062
Sklar (PI)
07/01/07- 06/30/12
Force, conformation & affinity in VLA-4 and LFA-1 adhesion
The goal of the project is to study adhesion in leukocyte cell models.
Role: Investigator
Oxnard Foundation Award
Chigaev (PI)
01/01/12-12/31/13
VLA-4 allosteric antagonists for hematological malignancies
The goal of the project is to improve treatment for hematological malignancies by testing a group of off-patent
drugs that exhibit properties of VLA-4 integrin allosteric antagonists and show promise as anti-cancer agents.
Role: PI
5P50 GM085273-03
Oliver (PI)
08/01/09-07/31/14
Center for the spatiotemporal modeling of cell signaling networks (STMC)
This grant supports a cross-campus, inter-institutional National Systems Biology Center, with participants from
NM, Los Alamos and Sandia National Laboratories.
Role: Investigator
Completed Research Support
NIH Technology Center for Networks
and Pathways
Waggoner (PI)
08/01/08-07/31/10
Carnegie-Mellon University Sklar (Subcontract PI)
NIH Driving Biological Project
Real-tome FAP-based FRET analysis of VLA-4 intramolecular conformation
The goal of the project was to use fluoragen activated proteins to measure integrin conformation.
Role: Investigator
C-2297-RAC
Chigaev (PI)
03/01/07-02/28/08
Research allocation committee grant from the dedicated health research funds from the University of New
Mexico SOM
GPCRs regulate both integrin adhesion and de-adhesion
Goals of this project were to perform a quantitative characterization of the VLA-4 integrin affinity states
generated after cell activation through Gs-coupled GPCRs, and to evaluate the role of the Gs-coupled
signaling in the regulation of cell adhesion in VLA-4/VCAM-1 specific model system.
Role: PI
PHS 398/2590 (Rev. 11/07)
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